$2.7 Million to Predict Safety and Effectiveness of Blood Thinners

Washington University School of Medicine in St. Louis
Friday, 5 December 2003

All blood thinners aren't equal; neither is their effect on patients with atrial fibrillation, the most common type of abnormal heart rhythm.

To determine how clinical and genetic factors predict a patient's response to therapy, a multi-disciplinary team led by researchers at Washington University School of Medicine in St. Louis has received a four-year, $2.7 million grant from the National Heart, Lung and Blood Institute.

Two main concerns for patients with atrial fibrillation are stroke and bleeding. People with this type of abnormal heart rhythm are five times more likely to develop a stroke than normal, according to Brian F. Gage, M.D. But the use of potent blood thinners to prevent complications such as strokes could be dangerous for patients at risk for excessive bleeding.

"Right now everyone with this condition is treated generically, regardless of genetic or clinical factors that might increase the risk for stroke or bleeding," says Gage, associate professor of medicine and principal investigator for this study. "We'd like to be able to predict the right dose of the right drug for the right patient. To do that, we need to determine in advance who is likely to develop a stroke, heart attack or hemorrhage."

In a pilot study with 400 patients (currently in press in the journal Thrombosis and Haemostasis), Gage's team found variations in response to treatment were attributable to genetic factors about 10 percent of the time and clinical and demographic factors about 30 percent of the time.

"These preliminary results tell us there are a lot of different factors influencing the risk for stroke and bleeding," Gage explains. "We need a comprehensive, interdisciplinary approach to study this issue."

To that end, Gage is collaborating with a multi-disciplinary team at the University, including Charles S. Eby, M.D., associate professor of medicine and of pathology and immunology; Howard L. McLeod, Pharm.D., associate professor of genetics, of medicine and of molecular biology and pharmacology; Thomas G. Cole, Ph.D., research professor of medicine; Robert C. Culverhouse, Ph.D., instructor in medicine; Deepak Voora, M.D., internal medicine resident; and Paul E. Milligan, Pharm.D., clinical pharmacist.

The team also is working with investigators at Duke University, Boston University, Brigham and Women's Hospital, Stanford University and the Veterans Affairs.

Based on their pilot study data, the group will refine and validate an algorithm they developed for determining the right dose of the blood thinner warfarin. They also will collect blood samples and clinical information from nearly 3,000 patients with atrial fibrillation who are taking warfarin or aspirin. By following these patients, the team hopes to determine which genetic and clinical factors cause such adverse events as stroke, heart attack or hemorrhage.

Funding from the National Heart, Lung and Blood Institute.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

For more information, or to contact Washington University School of Medicine in St. Louis, see their website at: medschool.wustl.edu